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Abstract Background The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. Methods Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. Results A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2–78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3–46.7, P

Abstract Background Globally increasing atmospheric nitrogen (N) deposition has altered soil phosphorus (P) transformations and availability, and thereby influenced structure and function of terrestrial ecosystems. Edaphic characteristics and chemical form of deposited N could be important factors determining impacts of N deposition on soil P transformations, yet the underlying mechanisms remain largely unknown. Objectives of this study were to examine how mineral-N and amino N differently affect P fractions, and identify key soil properties determining N addition impacts on soil P transformations. Considering that amino N is an important component of deposited N and forest soils vary greatly in different regions, the results of present study can guide the management of forests across different soils under ongoing N deposition scenarios. Methods We conducted a 60-day laboratory experiment to investigate the effects of N addition (NH4NO3 and glycine) on soil P fractions and related biochemical properties in four representative forest soils (brown, yellow brown, aeolian sandy, and red soils) in China. Glycine and NH4NO3 were separately added at three rates (5, 10 and 20 g N m–2 yr–1). Results Firstly, the percent changes in organic P fractions with N addition were significantly greater than changes in inorganic P fractions across all soils. Secondly, the percent changes in P fractions with glycine and NH4NO3 additions were significantly correlated across all soils and treatments. However, glycine addition had significantly greater impacts on organic P fractions than NH4NO3 addition in the aeolian sandy and red soils with low organic carbon content. Thirdly, P fractions responded differently to N addition among the four soils. N-induced changes in microbial biomass and phosphatase activities, pH, exchangeable Ca2+ and Mg2+ contributed differently to the changes in P fractions with N addition in the four soils. Conclusions The different responses of P fractions to N addition in the four soils were mainly generated by the differences in extent of microbial N limitation, acid buffering capacity, and cation exchange capacity among the soils. The different impacts of mineral and amino N on soil P fractions can be ascribed to their divergent effects on soil pH, microbial biomass and activities.

Abstract Hexavalent chromium (Cr(VI)) is still a common contaminant in water. In this work, we studied the Cr(VI) adsorption by polyphenol-rich bacterial cellulose(BC) gel, synthesized by the Komagataeibacter rhaeticus K15 using wine pomace. The results showed that the equilibrium removal capacity was 473.09 ± 1.41 mg g−1 (dry weight). The quasi-second-order kinetics model and the Langmuir removal isotherm model was the most suitable for describing the Cr(VI) removal process. Toxic Cr(VI) was converted to the low toxic Cr(III) during the removal process via the reduction of Cr(VI) to Cr(III) by polyphenols released into the solution by the BC gel. The FTIR, XRD, XPS, SEM-EDX results indicated the physical adsorption on the surface of BC and the reduction reaction between polyphenol groups and Cr(VI) is the critical mechanism of Cr(VI) removal by BC. The finding of this study demonstrates that polyphenols-rich BC gel produced from wine pomace has a superior feature for future Cr(VI)-wastewater purification.

Objectives: This study aimed to describe the lineage-specific transmissibility and epidemiological migration of Mycobacterium tuberculosis in China. Methods: We curated a large set of whole-genome sequences from 3204 M. tuberculosis isolates, including thousands of newly sequenced genomes, and applied a series of metrics to compare the transmissibility of M. tuberculosis strains between lineages and sublineages. The countrywide transmission patterns of major lineages were explored. Results: We found that lineage 2 (L2) was the most prevalent lineage in China (85.7%), with the major sublineage 2.2.1 (80.9%), followed by lineage 4 (L4) (13.8%), which comprises major sublineages 4.2 (1.5%), 4.4 (6.2%) and 4.5 (5.8%). We showed evidence for frequent cross-regional spread and large cluster formation of L2.2.1 strains, whereas L4 strains were relatively geographically restricted in China. Next, we applied a series of genomic indices to evaluate M. tuberculosis strain transmissibility and uncovered higher transmissibility of L2.2.1 compared with the L2.2.2 and L4 sublineages. Phylogeographic analysis showed that southern, eastern, and northern China were highly connected regions for countrywide L2.2.1 strain spread. Conclusions: The present study provides insights into the different transmission and migration patterns of the major M. tuberculosis lineages in China and highlights that transmissible L2.2.1 is a threat to tuberculosis control.

BackgroundMembranous nephropathy (MN) is an autoimmune disease and represents the most prevalent type of renal pathology in adult patients afflicted with nephrotic syndrome. Despite substantial evidence suggesting a possible link between MN and cancer, the precise underlying mechanisms remain elusive.MethodsIn this study, we acquired and integrated two MN datasets (comprising a single-cell dataset and a bulk RNA-seq dataset) from the Gene Expression Omnibus database for differential expression gene (DEG) analysis, hub genes were obtained by LASSO and random forest algorithms, the diagnostic ability of hub genes was assessed using ROC curves, and the degree of immune cell infiltration was evaluated using the ssGSEA function. Concurrently, we gathered pan-cancer-related genes from the TCGA and GTEx databases, to analyze the expression, mutation status, drug sensitivity and prognosis of hub genes in pan-cancer.ResultsWe conducted intersections between the set of 318 senescence-related genes and the 366 DEGs, resulting in the identification of 13 senescence-related DEGs. Afterwards, we meticulously analyzed these genes using the LASSO and random forest algorithms, which ultimately led to the discovery of six hub genes through intersection (PIK3R1, CCND1, TERF2IP, SLC25A4, CAPN2, and TXN). ROC curves suggest that these hub genes have good recognition of MN. After performing correlation analysis, examining immune infiltration, and conducting a comprehensive pan-cancer investigation, we validated these six hub genes through immunohistochemical analysis using human renal biopsy tissues. The pan-cancer analysis notably accentuates the robust association between these hub genes and the prognoses of individuals afflicted by diverse cancer types, further underscoring the importance of mutations within these hub genes across various cancers.ConclusionThis evidence indicates that these genes could potentially play a pivotal role as a critical link connecting MN and cancer. As a result, they may hold promise as valuable targets for intervention in cases of both MN and cancer.

Objective: This study aimed to investigate the mechanism of long noncoding ribonucleic acid (lncRNA) SNHG16 on kidney clear cell carcinoma (KIRC) cells by targeting miR-506-3p/ETS proto-oncogene 1, transcription factor (ETS1)/RAS/Extracellular regulated protein kinases (ERK) molecular axis, thus to provide reference for clinical diagnosis and treatment of KIRC in the future. Methods: Thirty-six patients with KIRC were enrolled in this study, and their carcinoma tissues and adjacent tissues were obtained for the detection of SNHG16/miR-506-3p/ETS1/RAS/ERK expression. Then, over-expressed SNHG16 plasmid and silenced plasmid were transfected into KIRC cells to observe the changes of their biological behavior. Results: SNHG16 and ETS1 were highly expressed while miR-506- 3p was low expressed in KIRC tissues; the RAS/ERK signaling pathway was significantly activated in KIRC tissues (P

Papilionoideae is the most species-rich subfamily of the third largest angiosperm family Fabaceae. One constituent large group, the inverted-repeat-lacking clade (IRLC), is well-known for the broad loss of one IR copy. Accumulating observations of massive plastomic disparities have made IRLC a well-suited model for exploring plastome evolution. However, there is still a large amount left to explore. The present study focused on the plastid tRNA (pttRNA) evolution within Papilionoideae, employing the currently densest sampling strategies for both the IRLC (156) and non-IRLC (109) lineages. Strikingly, our results revealed abundant inter-lineage variabilities in both tRNA sequences and structures, including a 3 nt difference in the average size of trnS-UGA, the consensus sequence disparities across 29 tRNAs, the distinct 3 nt indels in trnA-UGC, and an impressive 248 nt intron loss of IRLC trnI-GAU (potential markers). Additionally, there was unequal stability of the atypical secondary structures in trnS-GGA and trnS-UGA, as well as significantly diverse compositions of substitution events in all compared tRNAs (p < 0.05). Ultimately, these findings not only demonstrate the significant differences and unique markers of IRLC pttRNAs compared to other non-IRLC Papilionoideae, but also draw an important conclusion that the large losses of one IR potentially promote highly diverse evolutionary patterns of IRLC, which could partly compensate for the potential IR-lacking impacts.

Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 μg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1β, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1β. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N6-methyladenosine (m6A) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the m6A reader YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an m6A-YTHDF2-dependent manner.

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Background: The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. Methods: Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. Results: A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2–78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3–46.7, P < 0.001) and mycobacterial culture (54.2%, 95% CI 48.4–59.9, P < 0.001). When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis, cf-TB testing showed a sensitivity of 46.8% (450/961, 95% CI 43.7–50.0), significantly higher than both Xpert (116/961, 12.1%, 95% CI 10.2–14.3, P < 0.001) and mycobacterial culture (154/961, 16.0%, 95% CI 13.8–18.5, P < 0.001). The specificities of cf-TB testing, Xpert, and mycobacterial culture were all 100.0%. Conclusions: The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods, indicating that it can be considered as the primary diagnostic approach for improving TP detection. Trial registration The trial was registered on Chictr.org.cn (ChiCTR2000031680, https://www.chictr.org.cn/showproj.html?proj=49316). [ABSTRACT FROM AUTHOR]

In order to improve the mechanical properties and thermal stability of nylon 66 (PA66) and make it widely used in the field of automotive lightweight, 5%~20% carbon fiber (CF) was doped in PA66 matrix. The results show that the PA66 composite doped with 15% CF has better comprehensive properties than the unmodified PA66 material. The universal testing machine test shows that the tensile strength of PA66/15% CF is 180 MPa, increased by 177%, and the elastic modulus is 19 867 MPa, increased by 7.1 times. The bending strength is 262 MPa, which is increased by 212%, and the bending modulus is 15 867 MPa, increased by 6.4 times. The impact strength of PA66/15%CF is 12.7 kJ/m², which increases by 49.4%. The mass residual rate of PA66/15%CF composite is 22.8%, and the thermal stability of the material is significantly improved. The study indicates that CF-modified PA66 composites have the potential for use in the field of automotive light weighting, with a 15% doping amount being preferable. [ABSTRACT FROM AUTHOR]

The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer (NSCLC). Although researchers have disclosed that interleukin 17 (IL-17) can increase matrix metalloproteinases (MMPs) induction causing NSCLC cell metastasis, the underlying mechanism remains unclear. In the study, we found that IL-17 receptor A (IL-17RA), p300, p-STAT3, Ack-STAT3, and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17. p300, STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3, Ack-STAT3 and MMP19 level as well as the cell migration and invasion. Mechanism investigation revealed that STAT3 and p300 bound to the same region (-544 to -389 nt) of MMP19 promoter, and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity, p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17. Meanwhile, p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact, synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion. Besides, the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300, STAT3 or MMP19 gene plus IL-17 treatment, the nodule number, and MMP19, Ack-STAT3, or p-STAT3 production in the lung metastatic nodules were all alleviated. Collectively, these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation, which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to develop a model to predict World Health Organization/International Society of Urological Pathology (WHO/ISUP) low-grade or high-grade clear cell renal cell carcinoma (ccRCC) using 3D multiphase enhanced CT radiomics features (RFs). Methods CT data of 138 low-grade and 60 high-grade ccRCC cases were included. RFs were extracted from four CT phases: non-contrast phase (NCP), corticomedullary phase, nephrographic phase, and excretory phase (EP). Models were developed using various combinations of RFs and subjected to cross-validation. Results There were 107 RFs extracted from each phase of the CT images. The NCP-EP model had the best overall predictive value (AUC = 0.78), but did not significantly differ from that of the NCP model (AUC = 0.76). By considering the predictive ability of the model, the level of radiation exposure, and model simplicity, the overall best model was the Conventional image and clinical features (CICFs)-NCP model (AUC = 0.77; sensitivity 0.75, specificity 0.69, positive predictive value 0.85, negative predictive value 0.54, accuracy 0.73). The second-best model was the NCP model (AUC = 0.76). Conclusions Combining clinical features with unenhanced CT images of the kidneys seems to be optimal for prediction of WHO/ISUP grade of ccRCC. This noninvasive method may assist in guiding more accurate treatment decisions for ccRCC. Advances in knowledge This study innovatively employed stability selection for RFs, enhancing model reliability. The CICFs-NCP model's simplicity and efficacy mark a significant advancement, offering a practical tool for clinical decision-making in ccRCC management. [ABSTRACT FROM AUTHOR]

Objective lo explore the application value ot a recombinant antigen-based capture enzyme immunoassay (KAg-CEIA) in detection of recent human immunodeficiency virus type 1 (HIV-1) infection in the sentinel surveillance population. Methods Among the HIV/AIDS sentinel surveillance population in Yunnan province in 2015, the confirmed HIV-1 antibodies positive plasma specimens matching the detection criteria for recent HIV-1 infection were tested by HIV-1 RAg-CEIA. The recent HIV-1 infection specimens were classified by the normalized optical density (ODn) values, and then the HIV-1 incidence in population were estimated. The detection and analysis data were compared with those by BED capture enzyme immunoassay (BED-CEIA) and limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA), respectively. Results A total of 51 313 plasma specimens were tested for HIV antibodies, in which 1 255 specimens were HIV-1 antibodies positive. 253 out of 373 specimens matching the detection criteria for recent HIV-1 infection were tested by the 3 assays, respectively. By RAg-CEIA, BED-CEIA and LAg-Avidity EIA, 88, 78 and 54 specimens were classified as recent HIV-1 infections, and the HIV-1 incidence in the sentinel surveillance population was 0.33% (95% CI: 0.26%~0.39%), 0.31% (95% CI: 0.24%-0.38%) and 0.31% (95% CI: 0.22%-0.39%), respectively. The differences between the HIV-1 incidence by the 3 assays were not statistically significant (P = 0.927). Among the sub-populations, the HIV-1 incidence in men who have sex with men (MSM) were 3.50% (95% CI: 2.48%-4.52%), 3.92% (95% CI: 2.76%-5.08%) and 4.17% (95% CI: 2.79%-5.55%), respectively. The differences between the HIV-1 incidence by the 3 assays were not statistically significant (P = 0.763). The ODn values by RAg-CEIA were linear correlation with those by BED-CEIA (Spearman's rank correlation coefficient was 0.911), and those by LAg-Avidity EIA (Spearman' s rank correlation coefficient was 0.755), respectively. Conclusion HIV-1 RAg-CEIA can be effectively used in classification of recent HIV-1 infections and estimation of HIV-1 incidence, indicating that this approach has a good application prospect in detection of recent HIV-1 infection. [ABSTRACT FROM AUTHOR]

In the design and development of high voltage distribution box, the flatness of installation surface directly affects the installation accuracy, anti-fatigue performance and sealing performance. Aiming at the problem that the flatness of the installation surface of a high voltage distribution box is unqualified under the initial process, the injection molding process was simulated by computer aided engineering technology, and the orthogonal test was designed to explore the process optimization scheme of flatness. The results show that the influence of holding time on flatness is extremely significant, the influence of barrel temperature and mold surface temperature on flatness is significant, and the influence of injection time on flatness is not significant. The optimum combination of process parameters is A2B3C1D3. The simulation results of the optimized process show that the flatness is reduced from 2.756 9 mm to 1.532 9 mm, and the optimization rate reaches 44.4%, which meets the design requirements. The filling process, shrinkage mark, welding line and injection pressure results also meet the requirements. The appearance and flatness of the samples are qualified by the optimized process, which verifies the feasibility of the optimized process. [ABSTRACT FROM AUTHOR]

This paper mainly focuses on the development of a learning-based controller for a class of uncertain mechanical systems modeled by the Euler-Lagrange formulation. The considered system can depict the behavior of a large class of engineering systems, such as vehicular systems, robot manipulators and satellites. All these systems are often characterized by highly nonlinear characteristics, heavy modeling uncertainties and unknown perturbations, therefore, accurate-model-based nonlinear control approaches become unavailable. Motivated by the challenge, a reinforcement learning (RL) adaptive control methodology based on the actor-critic framework is investigated to compensate the uncertain mechanical dynamics. The approximation inaccuracies caused by RL and the exogenous unknown disturbances are circumvented via a continuous robust integral of the sign of the error (RISE) control approach. Different from a classical RISE control law, a tanh($) function is utilized instead of a sign($) function to acquire a more smooth control signal. The developed controller requires very little prior knowledge of the dynamic model, is robust to unknown dynamics and exogenous disturbances, and can achieve asymptotic output tracking. Eventually, co-simulations through ADAMS and MATLAB/Simulink on a three degrees-of-freedom (3-DOF) manipulator and experiments on a real-time electromechanical servo system are performed to verify the performance of the proposed approach. [ABSTRACT FROM AUTHOR]

High‐risk populations are the predominant populations affected by hepatitis C virus (HCV) infection, and there is an urgent need for efficient and cost‐effective HCV testing strategies for high‐risk populations to identify potential undiagnosed HCV‐infected individuals. This study compared several commonly used testing strategies and conducted effectiveness and cost analysis to select the appropriate testing strategy for diagnosing HCV infection in high‐risk populations. Among the 2093 samples from high‐risk populations in this study, 1716 were HCV negative, 237 were current HCV infection, 137 were past HCV infection, and three were acute early HCV infection. It was found that out of 237 patients with HCV current infection, Strategy A could detect 225 cases, with a missed detection rate of 5.06%, and the total cost was 33 299 RMB. In addition, Strategy B could detect 237 cases of current HCV infection, and the HCV missed detection rate was 0.00%, and the total cost was 147 221 RMB. While 137 cases of past HCV infection could be distinguished by strategy C, but 14 cases with current HCV infection were missed, with an HCV‐positive missed detection rate of 5.91%, and the total cost for Strategy C was 43 059 RMB. In conclusion, in high‐risk populations, the HCV positivity rate is typically higher. If feasible, the preferred approach is to directly conduct HCV RNA testing, which effectively minimizes the risk of missing cases. However, in situations with limited resources, it is advisable to initially choose a highly sensitive method for anti‐HCV screening, followed by HCV RNA testing on reactive samples. [ABSTRACT FROM AUTHOR]

Introduction: Major depressive disorder (MDD) affects about 17% population in the world. Although abnormal energy metabolism plays an important role in the pathophysiology of MDD, however, how deficiency of adenosine triphosphate (ATP) products affects emotional circuit and what regulates ATP synthesis are still need to be elaborated. Aims: Our study aimed to investigate how deficiency of PGAM5‐mediated depressive behavior. Results: We firstly discovered that PGAM5 knockout (PGAM5−/−) mice generated depressive‐like behaviors. The phenotype was reinforced by the observation that chronic unexpected mild stress (CUMS)‐induced depressive mice exhibited lowered expression of PGAM5 in prefrontal cortex (PFC), hippocampus (HIP), and striatum. Next, we found, with the using of functional magnetic resonance imaging (fMRI), that the functional connectivity between PFC reward system and the PFC volume were reduced in PGAM5−/− mice. PGAM5 ablation resulted in the loss of dendritic spines and lowered density of PSD95 in PFC, but not in HIP. Finally, we found that PGAM5 ablation led to lowered ATP concentration in PFC, but not in HIP. Coimmunoprecipitation study showed that PGAM5 directly interacted with the ATP F1F0 synthase without influencing the interaction between ATP F1F0 synthase and Bcl‐xl. We then conducted ATP administration to PGAM5−/− mice and found that ATP could rescue the behavioral and neuronal phenotypes of PGAM5−/− mice. Conclusions: Our findings provide convincing evidence that PGAM5 ablation generates depressive‐like behaviors via restricting neuronal ATP production so as to impair the number of neuronal spines in PFC. [ABSTRACT FROM AUTHOR]

We performed a meta‐analysis to compare the effect of preoperative and postoperative radiotherapy on wound complications after resection of extremity soft tissue sarcoma (ESTS). A comprehensive computerised search of the PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases was conducted from their inception to August 2023 to identify studies comparing the effect of preoperative and postoperative radiotherapy on wound complications after ESTS resection. Two investigators independently screened the literature, extracted the data, and assessed the quality of the articles. The meta‐analysis was performed using RevMan 5.4 software. Nine studies with 1271 patients were included, with 631 and 640 patients in the preoperative and postoperative radiotherapy groups, respectively. The results showed that the incidence of postoperative wound complications after ESTS resection was significantly higher with preoperative radiotherapy than with postoperative radiotherapy (27.26% vs. 12.03%, odds ratio [OR]: 2.88, 95% confidence interval [CI]: 2.12–3.91, p < 0.001). However, the rate of local recurrence of ESTS was significantly lower with preoperative radiotherapy than with postoperative radiotherapy (8.75% vs. 14.81%, OR: 0.57, 95% CI: 0.36–0.91, p = 0.02), and the 3‐year overall survival was significantly higher in the preoperative radiotherapy group than in the postoperative radiotherapy group (82.24% vs. 70.04%, OR: 1.97, 95% CI: 1.05–3.71, p = 0.03). This pooled analysis suggests that although preoperative radiotherapy increases the rate of wound complications in ESTS compared with postoperative radiotherapy, it significantly reduces the rate of local recurrence after ESTS resection and improves the overall survival of patients. Owing to the limitations in the number and quality of the included studies, additional prospective cohort studies or randomised controlled trials are required to confirm these findings. [ABSTRACT FROM AUTHOR]

After drawing comparisons between the reaction pathways of cytochrome c oxidase (CcO, Complex 4) and the preceding complex cytochrome bci (Complex 3), both being proton pumping complexes along the electron transport chain, we provide an analysis of the reaction pathways in bacterial ba3 class CcO, comparing spectroscopic results and kinetics observations with results from DFT calculations. For an important arc of the catalytic cycle in CcO, we can trace the energy pathways for the chemical protons and show how these pathways drive proton pumping of the vectorial protons. We then explore the proton loading network above the Fe heme a3-CuB catalytic center, showing how protons are loaded in and then released by combining DFT-based reaction energies with molecular dynamics simulations over states of that cycle. We also propose some additional reaction pathways for the chemical and vector protons based on our recent work with spectroscopic support. [ABSTRACT FROM AUTHOR]

The article focuses on investigating the impact of the COVID-19 pandemic on otorhinolaryngology (ENT) residency training at Tan Tock Seng Hospital in Singapore. Topics include the reduction in surgical training opportunities, disruptions to educational routines, and the psychological distress experienced by ENT residents during the pandemic. It reports that the pandemic led to a decline in operative load and outpatient clinic consultations for residents.

Glycogen synthase kinase‐3α/β (GSK3α/β) is a critical kinase for Tau hyperphosphorylation which contributes to neurodegeneration. Despite the termination of clinical trials for GSK3α/β inhibitors in Alzheimer's disease (AD) treatment, there is a pressing need for novel therapeutic strategies targeting GSK3α/β. Here, we identified the compound AS1842856 (AS), a specific forkhead box protein O1 (FOXO1) inhibitor, reduced intracellular GSK3α/β content in a FOXO1‐independent manner. Specifically, AS directly bound to GSK3α/β, promoting its translocation to the multivesicular bodies (MVBs) and accelerating exocytosis, ultimately decreasing intracellular GSK3α/β content. Expectedly, AS treatment effectively suppressed Tau hyperphosphorylation in cells exposed to okadaic acid or expressing the TauP301S mutant. Furthermore, AS was visualized to penetrate the blood–brain barrier (BBB) using an imaging mass microscope. Long‐term treatment of AS enhanced cognitive function in P301S transgenic mice by mitigating Tau hyperphosphorylation through downregulation of GSK3α/β expression in the brain. Altogether, AS represents a novel small‐molecule GSK3α/β inhibitor that facilitates GSK3α/β exocytosis, holding promise as a therapeutic agent for GSK3α/β hyperactivation‐associated disorders. [ABSTRACT FROM AUTHOR]

The ectoparasites of rodents and other small mammals usually involve five categories of arthropods-fleas, sucking lice, gamasid mites, chigger mites, and occasionally, ticks. These ectoparasites are medically important, serving as vectors for diseases such as plague, murine typhus, scrub typhus, forest encephalitis, Lyme disease, and other zoonoses. Field surveys, collection, and specimen preparation of ectoparasites are crucial for studying taxonomy, faunistics, ecology, and epidemiology. They are also essential for vector surveillance. The present protocol summarizes the on-site monitoring and specimen-making of ectoparasites of rodents and other sympatric small mammals. Besides the collection and specimen preparation of small mammal hosts, the protocol describes in detail the collection, fixation, specimen-making, and taxonomic identification of ectoparasites and provides some monitoring indices. The on-site monitoring indices include the host density index and the infestation indices of ectoparasites (prevalence, mean abundance, mean intensity). The methodologies outlined in this protocol provide technical guidance and references for vector monitoring (surveillance) and control. Key features • Collection and specimen preparation of small mammal hosts, including rodents (rats, mice, and voles) and other sympatric small mammals (shrews, tree shrews, and pikas). • Collection, fixation, specimen-making, and taxonomic identification of ectoparasites, including fleas, sucking lice, gamasid mites, chigger mites, and ticks. • On-site monitoring indices-host density index and infestation indices of ectoparasites: prevalence, mean abundance, and mean intensity. Graphical overview Flowchart for collection and specimen-making of ectoparasites and their hosts. A. Process for the collection and specimen preparation of small mammal hosts. B. Collection and fixation of ectoparasites. C. Process for specimen-making for different categories of ectoparasites., Competing Interests: Competing interestsThe authors declare they have no conflict of interest., (©Copyright : © 2024 The Authors; This is an open access article under the CC BY-NC license.)

Prior research has suggested an inverse correlation between dried fruit intake and type 2 diabetes mellitus (T2DM), yet the causal link remains uncertain. This study seeks to investigate the potential causal impact of dried fruit intake on T2DM, covering cases both with and without various complications, as well as glycaemic traits, using a two-sample Mendelian randomisation (MR) approach. Using MR analysis with genome-wide association study summary statistics, the primary analysis investigated the causal relationship between dried fruit intake and T2DM, both with and without complications, as well as glycaemic traits, employing the inverse variance weighted method. Supplementary analyses were conducted using MR-Egger and the weighted median method. Heterogeneity and intercept tests were utilised to evaluate the robustness of the study outcomes. The results show a significant association between dried fruit intake and T2DM without complications, as well as fasting insulin. Sensitivity analyses confirmed the robustness of the results and the independence from multicollinearity. However, no association was found between dried fruit intake and T2DM with various complications or other glycaemic traits. The significant association between dried fruit intake and T2DM without complications and fasting insulin persisted even after adjusting for BMI. This study offers genetic evidence endorsing the protective effects of dried fruit intake against T2DM, specifically for cases without complications, and in regulating fasting insulin. These findings suggest that dried fruit intake might serve as a primary preventive strategy for T2DM.

Abstract: Neuropathic pain is a pervasive medical challenge currently lacking effective treatment options. Molecular changes at the site of peripheral nerve injury contribute to both peripheral and central sensitization, critical components of neuropathic pain. This study explores the role of the G-protein-coupled bile acid receptor (GPBAR1 or TGR5) in the peripheral mechanisms underlying neuropathic pain induced by partial sciatic nerve ligation in male mice. TGR5 was upregulated in the injured nerve site and predominantly colocalized with macrophages. Perisciatic nerve administration of the TGR5 agonist, INT-777 according to a prevention protocol (50 μg/μL daily from postoperative day [POD] 0 to POD6) provided sustained relief from mechanical allodynia and spontaneous pain, whereas the TGR5 antagonist, SBI-115 worsened neuropathic pain. Transcriptome sequencing linked the pain relief induced by TGR5 activation to reduced neuroinflammation, which was further evidenced by a decrease in myeloid cells and pro-inflammatory mediators (eg, CCL3, CXCL9, interleukin [IL]-6, and tumor necrosis factor [TNF] α) and an increase in CD86-CD206+ anti-inflammatory macrophages at POD7. Besides, myeloid-cell-specific TGR5 knockdown in the injured nerve site exacerbated both neuropathic pain and neuroinflammation, which was substantiated by bulk RNA-sequencing and upregulated expression levels of inflammatory mediators (including CCL3, CCL2, IL-6, TNF α, and IL-1β) and the increased number of monocytes/macrophages at POD7. Furthermore, the activation of microglia in the spinal cord on POD7 and POD14 was altered when TGR5 in the sciatic nerve was manipulated. Collectively, TGR5 activation in the injured nerve site mitigates neuropathic pain by reducing neuroinflammation, while TGR5 knockdown in myeloid cells worsens pain by enhancing neuroinflammation., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

CD8 + T cells play pivotal roles in combating intracellular pathogens and eliminating malignant cells in cancer. However, the prognostic role of CD8 + T cells in ovarian carcinoma is insufficiently exploited. Herein, through univariate Cox regression along with least absolute shrinkage and selection operator (LASSO) regression analyses, we developed a novel prognostic model based on CD8 + T cell markers identified by single-cell sequencing (scRNA-seq) analyses. Patient grouping by the median risk score reveals an excellent prognostic efficacy of this model in both training and validation cohorts. Of note, patients classified as low-risk group exhibit a dramatically improved prognosis. In addition, higher enrichment level of immune-related pathways and increased infiltration level of multiple immune cells are found in patients with lower risk score. Importantly, low-risk patients also exhibited higher response rate to immunotherapies. Summarily, this developed CD8 + T cell-associated prognostic model serves as an excellent predictor for clinical outcomes and aids in guiding therapeutic strategy choices for ovarian cancer patients.